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1.
Int J Clin Pract ; : e14505, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196443

RESUMO

AIMS: To evaluate polypharmacy-related problems in the elderly people who live in rural through a proactive pharmaceutical care project under a novel remote medical service infrastructure (the Houston-Apollo polypharmacy project). METHODS: It is a prospectively cross-sectional study. The elderly aged 65 years old lived in communities executed the congregate meal service and joined the Houston-Apollo project were included. During March and July on 2020, the pharmaceutical care team of Houston-Apollo polypharmacy project interviewed old people and collected their medications by remote video. Polypharmacy situation and drug-related problems, including potentially inappropriate medications (PIMs), anticholinergic burden (ACB) and risk of sarcopaenia, were evaluated by clinical pharmacists. In addition, we analysed the categories of the prescription types between polypharmacy and non-polypharmacy users, polypharmacy users with and without PIMs or ACB. A patient-specific integrated pharmacist's note for medication education and a dear doctor letter (as needed) were generated and delivered within 2-weeks postinterviewed. Age- and sex-adjusted logistic regression model was used to evaluate the association between polypharmacy and these potential medication problems. RESULTS: There were 87 older people (mean age = 75.9) and 536 long-term medications were collected. Among them, 52% were defined as polypharmacy users. Polypharmacy was significantly associated with higher risk of PIMs and ACB. The adjusted odd ratio was 5.31 (95% CI: 2.02-13.9) and 10.1 (95% CI: 3.4-29.7), respectively. Among polypharmacy users, there were nearly double the prescriptions for the nervous system and musculoskeletal system among patients with PIMs compared with those without PIMs. Besides, polypharmacy users with ACB showed higher rate of prescriptions for the nervous system and the alimentary tract and metabolism system compared with those without ACB. CONCLUSION: Polypharmacy was significantly associated with negative impact of medication safety among the elderly people in rural area. A persistent remote pharmaceutical care intervention was crucial for improving this problem.

2.
J Nanosci Nanotechnol ; 21(12): 5912-5919, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229786

RESUMO

Chitosan (CS), the only alkaline polysaccharose available in nature, has always been a promising candidate for drug delivery owing to its excellent biodegradability and biocompatibility. However, inherent solubility and polycationic properties of CS largely hinder electrospinning, which is an efficient method of fabricating nanofibers for drug carriers. To solve this problem and extend the applications of CS, polyamide/chitosan/tetraethyl orthosilicate (PA/CS/TEOS) composite nanofibers were successfully prepared as drug carriers in this study via electrospinning. The PA/CS/TEOS ratios significantly influenced the nanofiber morphology. As the content of each was increased, the beads among the membranes increased initially and then decreased, determined by scanning electron microscopy (SEM). The morphology of the optimum membranes with the ratio of 1:0.13:0.67 was smoother with less beads and uniform fiber diameter. Finally, the membranes with optimum ratios were used as carriers of ofloxacin in the study of drug release performance to identify their future feasibility, which revealed an initial fast release followed by a relatively stable release.


Assuntos
Quitosana , Nanofibras , Portadores de Fármacos , Nylons , Silanos
3.
Mol Cancer Res ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312289

RESUMO

MicroRNA-200c (miR-200c) is a tumor suppressor microRNA that plays a critical role in regulating epithelial phenotype and cancer stemness. p53 deficiency downregulates the expression of miR-200c and leads to epithelial-mesenchymal transition (EMT) and stemness phenotype, which contributes to the progression of breast cancers. In this study, we demonstrated that CRISPR-mediated knockout of miR-200c induces metabolic features similar to the metabolic rewiring caused by p53 hot-spot mutations, and that impairing this metabolic reprogramming interferes with miR-200c deficiency-induced stemness and transformation. Moreover, restoring miR-200c expression compromised EMT, stem cell properties, and the Warburg effect caused by p53 mutations, suggesting that mutant p53 induces EMT-associated phenotypes and metabolic reprogramming by downregulating miR-200c. Mechanistically, decreased expression of PCK2 was observed in miR-200c- and p53-deficient mammary epithelial cells, and forced expression of miR-200c restored PCK2 in p53 mutant-expressing cells. Reduced PCK2 expression not only led to attenuated oxidative phosphorylation (OXPHOS) and increased stemness in normal mammary epithelial cells but also compromised the enhanced OXPHOS and suppression of cancer stemness exerted by miR-200c in p53 mutation-bearing basal-like breast cancer (BLBC) cells. Clinically, PCK2 expression is negatively associated with EMT markers and is downregulated in basal-like subtype and cases with low miR-200c expression or p53 mutation. Notably, low expression of PCK2 is associated with poor overall survival in breast cancer patient. Implications: Together, our results suggest that p53 and miR-200c regulate OXPHOS and stem/cancer stemness through PCK2, and loss of the p53-miR-200c-PCK2 axis might provide metabolic advantages that facilitate cancer stemness, leading to the progression of BLBCs.

5.
Food Funct ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34308455

RESUMO

The role of supplementation with different Bacteroides fragilis (B. fragilis) strains in alleviating ulcerative colitis (UC) is unclear due to the controversial results from animal experiments. In this study, three B. fragilis strains were evaluated for their ability to alleviate dextran sulfate sodium (DSS)-induced UC in C57BL/6J mice. We analyzed the anti-inflammatory effects of different B. fragilis strains and the changes they caused in the intestinal microbiota composition, intestinal epithelial permeability, cytokine concentrations, protein expression of nuclear factor kappa-B (NF-κB) and the underlying specific genes. The results showed that when orally administered, the different B. fragilis strains exerted different effects on the assessed parameters of the mice. The results of real-time quantitative polymerase chain reaction and immunofluorescence staining showed that the supplementation of B. fragilis FSHCM14E1, but not FJSWX11BF, enhanced the expression of the tight-junction proteins ZO-1, occludin and claudin-1. Western blot analysis showed that the anti-inflammatory effects of B. fragilis FSHCM14E1 were related to the NF-κB pathway. Genomic analysis suggested that the anti-inflammatory effects of FSHCM14E1 may be mediated through specific genes associated with defense mechanisms and the secretion of SCFAs. Overall, this study indicates the therapeutic potential of B. fragilis FSHCM14E1 for the prevention of UC.

6.
FEBS J ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34310043

RESUMO

Cytoplasmic microbial and host aberrant DNAs act as danger signals and trigger host immune responses. Upon recognition, the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) catalyzes the production of a second messenger 2'3'-cGAMP, which activates endoplasmic reticulum (ER)-associated stimulator of interferon genes (STING) and ultimately leads to the induction of type I interferons and inflammatory genes that collectively initiate host immune defense against microbial invasion. Inappropriate activation or suppression of this signaling pathway has been implicated in the development of some autoimmune diseases, sterile inflammation and cancers. In this review, we describe how the activity of cGAS and STING is regulated by host post-translational modifications and summarize the recent advances of cell-specific cGAS-STING activation and its association in sterile inflammatory diseases. We also discuss key outstanding questions in the field, including how our knowledge of cGAS-STING pathway could be translated into clinical applications.

7.
J Insect Physiol ; 133: 104276, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34245800

RESUMO

The insect taste system regulates insect feeding behavior and patterns of food consumption. In this study, we showed that the medial and lateral sensilla styloconica in the mouthparts of 5th-instar Asian corn borer larvae are sensitive to fructose and sucrose in a concentration-dependent way. The two sensilla produced significant electrophysiological responses (greater than100 spikes/s) by exposure to 10 mM fructose or sucrose. However, electrophysiological responses and feeding preferences to fructose or sucrose were inhibited by neuropeptide F double-stranded RNA (dsNPF). Additionally, the medial sensilla styloconica are sensitive to low concentrations of the deterrents caffeine and nicotine. However, starvation, followed by increases in larval npf expression plus feeding, led to increases in spike frequencies of related sensilla to fructose, sucrose, and deterrents. In contrast, these responses were reduced on the dsNPF treatment. Our results suggest that NPF plays an important role influencing caterpillar feeding behavior through regulating the taste neurons of the sensilla styloconica.

8.
Stem Cell Res Ther ; 12(1): 379, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215331

RESUMO

BACKGROUND: Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear. METHODS: In this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro. RESULTS: We found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9+ cells. CONCLUSIONS: ESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.


Assuntos
Injúria Renal Aguda , Vesículas Extracelulares , Células-Tronco Mesenquimais , Injúria Renal Aguda/terapia , Animais , Células-Tronco Embrionárias , Rim , Camundongos
9.
Future Oncol ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254526

RESUMO

Aim: This study was conducted to evaluate the efficacy of immune checkpoint inhibitors (ICIs) plus anlotinib versus anlotinib alone to provide guidance for clinical treatment of non-small-cell lung cancer. Patients & methods: The records of 139 patients with advanced non-small-cell lung cancer who received at least one dose of ICIs plus anlotinib (IA group) or single-agent anlotinib (AA group) were retrospectively reviewed. The efficacy of the treatments, survival outcomes and adverse events were analyzed. The primary end point was investigator-assessed progression-free survival (PFS). Result: The IA group had a significantly prolonged median PFS (mPFS: 5.8 vs 4.2 months; p = 0.022) compared with the AA group (hazard ratio: 0.68; 95% CI: 0.68-0.97). In patients with brain metastases, the IA group exhibited improved efficacy (mPFS: 6.0 vs 3.8 months; p = 0.034) compared with the AA group (hazard ratio: 0.49; 95% CI: 0.23-1.05). Conclusion: ICIs plus anlotinib significantly improved efficacy compared with anlotinib alone and showed substantial potential for the control of intracranial lesions.

10.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206143

RESUMO

Primary liver cancer accounts for the third most deadly type of malignant tumor globally, and approximately 80% of the cases are hepatocellular carcinoma (HCC), which highly relies on the activity of hypoxia responsive pathways to bolster its metastatic behaviors. MicroRNA-29a (MIR29A) has been shown to exert a hepatoprotective effect on hepatocellular damage and liver fibrosis induced by cholestasis and diet stress, while its clinical and biological role on the activity hypoxia responsive genes including LOX, LOXL2, and VEGFA remains unclear. TCGA datasets were retrieved to confirm the differential expression and prognostic significance of all genes in the HCC and normal tissue. The Gene Expression Omnibus (GEO) dataset was used to corroborate the differential expression and diagnostic value of MIR29A. The bioinformatic identification were conducted to examine the interaction of MIR29A with LOX, LOXL2, and VEGFA. The suppressive activity of MIR29A on LOX, LOXL2, and VEGF was verified by qPCR, immunoblotting, and luciferase. The effect of overexpression of MIR29A-3p mimics in vitro on apoptosis markers (caspase-9, -3, and poly (ADP-ribose) polymerase (PARP)); cell viability and wound healing performance were examined using immunoblot and a WST-1 assay and a wound healing assay, respectively. The HCC tissue presented low expression of MIR29A, yet high expression of LOX, LOXL2, and VEGFA as compared to normal control. Serum MIR29A of HCC patients showed decreased levels as compared to that of normal control, with an area under curve (AUC) of 0.751 of a receiver operating characteristic (ROC) curve. Low expression of MIR29A and high expression of LOX, LOXL2, and VEGFA indicated poor overall survival (OS). MIR29A-3p was shown to target the 3'UTR of LOX, LOXL2, and VEGFA. Overexpression of MIR29A-3p mimic in HepG2 cells led to downregulated gene and protein expression levels of LOX, LOXL2, and VEGFA, wherein luciferase reporter assay confirmed that MIR29A-3p exerts the inhibitory activity via directly binding to the 3'UTR of LOX and VEGFA. Furthermore, overexpression of MIR29A-3p mimic induced the activity of caspase-9 and -3 and PARP, while it inhibited the cell viability and wound healing performance. Collectively, this study provides novel insight into a clinical-applicable panel consisting of MIR29, LOX, LOXL2, and VEGFA and demonstrates an anti-HCC effect of MIR29A via comprehensively suppressing the expression of LOX, LOXL2, and VEGFA, paving the way to a prospective theragnostic approach for HCC.


Assuntos
Aminoácido Oxirredutases/genética , Carcinoma Hepatocelular/genética , MicroRNAs/genética , Proteína-Lisina 6-Oxidase/genética , Fator A de Crescimento do Endotélio Vascular/genética , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Transdução de Sinais/genética
11.
Biochem Biophys Res Commun ; 568: 103-109, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34214874

RESUMO

At present, stem cell transplantation has a significant therapeutic effect on spinal cord injury (SCI), however, it is still challenging for the seed cells selection. In this study, in order to explore cells with wide neural repair potentials, we selected the pluripotent stem cells multilineage-differentiating stress-enduring (Muse) cells, inducing the in vitro differentiation of human Muse cells into neural precursor cells (Muse-NPCs) by applying neural induction medium. Here, we found induced Muse-NPCs expressed neural stem cell markers Nestin and NCAM, capable of differentiating into three types of neural cells (neuron, astrocyte and oligodendrocyte), and have certain biological functions. When Muse-NPCs were transplanted into rats suffering from T10 SCI, motor function was improved. These results provide an insight for application of Muse-NPCs in cell therapy or tissue engineering for the repair of SCI in future.

13.
Nat Nanotechnol ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34239120

RESUMO

The growth of connected intelligent devices in the Internet of Things has created a pressing need for real-time processing and understanding of large volumes of analogue data. The difficulty in boosting the computing speed renders digital computing unable to meet the demand for processing analogue information that is intrinsically continuous in magnitude and time. By utilizing a continuous data representation in a nanoscale crossbar array, parallel computing can be implemented for the direct processing of analogue information in real time. Here, we propose a scalable massively parallel computing scheme by exploiting a continuous-time data representation and frequency multiplexing in a nanoscale crossbar array. This computing scheme enables the parallel reading of stored data and the one-shot operation of matrix-matrix multiplications in the crossbar array. Furthermore, we achieve the one-shot recognition of 16 letter images based on two physically interconnected crossbar arrays and demonstrate that the processing and modulation of analogue information can be simultaneously performed in a memristive crossbar array.

14.
Anal Biochem ; : 114310, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34280371

RESUMO

Exposure to fine particulate matter (PM2.5) is closely related to lung diseases and has become more and more harmful to public health. The traditional Chinese medicine of Bletilla Striata has the effect of clearing and nourishing the lungs in clinics. The purpose of the study is using metabolomics methods to explore the mechanism of PM2.5-induced lung injury and Bletilla Striata's therapeutic effect. In this article, we used an Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UPLC-QTOF/MS) method to identify the potential biomarkers. The results showed that there were 18 differential metabolites in the plasma and urine of rats with PM2.5-induced lung injury, involving the glycerophospholipid metabolism pathway, the tryptophan metabolism pathway, and the purine metabolism pathway, etc. After the administration, Bletilla Striata changed the levels of 21 metabolites, and partly corrected the changes in the level of metabolites caused by PM2.5. The results indicated that Bletilla Striata could exert a good therapeutic effect by reversing the levels of some biomarkers in the rats with PM2.5-induced lung impairment.

15.
Clin Exp Nephrol ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34283324

RESUMO

BACKGROUND: Page kidney is a rare condition leading to secondary hypertension and encountered most frequently due to traumatic subcapsular hematoma. Here, we present a case of a 15-year-old boy with a history of Tourette syndrome, who had Page kidney hypertension secondary to subcapsular hematoma compression due to his self-injury behavior for many years.

16.
Opt Lett ; 46(14): 3484-3487, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264244

RESUMO

A new, to the best of our knowledge, method for directly measuring the skew angle of a Poynting vector of optical vortices is reported in this Letter. We design an incomplete optical vortex phase to mimic the occlusion of actual objects on the light path. By capturing the intensity cross section of the incomplete vortex field, the energy flow can be observed directly; thus, the skew angle of the Poynting vector can be directly measured. In this Letter, we measure the skew angle of the Poynting vector with an error less than 3%. Further, the work in this Letter may provide a new way to sense the translational distance and measure the topological charge of the optical vortex.

17.
Brain Res Bull ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34284074

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by irreversible cognitive deficits and memory dysfunction. Dopamine is the most abundant catecholaminergic neurotransmitter in the brain which regulates motivation, reward, movement, and cognition. Recently, increasing evidences have shown that dopaminergic system is disturbed in AD conditions, and pharmacological interventions targeting dopamine D1 receptor (DRD1) exhibit certain therapeutic benefits in AD models. However, the underlying link between DRD1 and AD remains elusive. This study sought to test whether the selective DRD1 agonist A-68930 could improve streptozotocin (STZ)-induced cognitive impairment in mice. Here we found that A-68930 treatment through intraperitoneal injection efficiently alleviated STZ-induced cognitive deficits in mice. Moreover, our mechanism researches revealed that the DRD1 signaling induced by A-68930 significantly rescued STZ-induced mitochondrial biogenesis deficit, mitochondrial dysfunction, Aß overexpression, and tau phosphorylation in mice hippocampus and cortex and SH-SY5Y cells, which may be mediated through stimulating AMPK/PGC-1α pathway. This study indicates that DRD1 agonist A-68930 can improve STZ-induced cognitive deficits and mitochondrial dysfunction in vivo and in vitro, and DRD1 may represent an appropriate target candidate for AD drug development.

18.
Arch Insect Biochem Physiol ; : e21830, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34288081

RESUMO

Zinc finger proteins (ZFPs) are a class of transcription factors that contain zinc finger domains and play important roles in growth, aging, and responses to abiotic and biotic stresses. These proteins activate or inhibit gene transcription by binding to single-stranded DNA or RNA and through RNA/DNA bidirectional binding and protein-protein interactions. However, few studies have focused on the oxidation resistance functions of ZFPs in insects, particularly Apis cerana. In the current study, we identified a ZFP41 gene from A. cerana, AcZFP41, and verified its function in oxidative stress responses. Real-time quantitative polymerase chain reaction showed that the transcription level of AcZFP41 was upregulated to different degrees during exposure to oxidative stress, including that induced by extreme temperature, UV radiation, or pesticides. In addition, the silencing of AcZFP41 led to changes in the expression patterns of some known antioxidant genes. Moreover, the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and glutathione S-transferase (GST) in AcZFP41-silenced honeybees were higher than those in a control group. In summary, the data indicate that AcZFP41 is involved in the oxidative stress response. The results provide a theoretical basis for further studies of zinc finger proteins and improve our understanding of the antioxidant mechanisms of honeybees.

19.
Insect Sci ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34297483

RESUMO

The fall armyworm Spodoptera frugiperda is a worldwide serious agricultural pest, and recently invades in South China. Sex pheromone can be employed to monitor its population dynamics accurately in the field. However, the pheromone components previously reported by testing different geographic populations and strains are not consistent. On the basis of confirming that the S. frugiperda population from Yunnan province belonged to the corn strain, we analyzed the potential sex pheromone components in the pheromone gland extracts of females using the gas chromatography coupled with electroantennographic detection (GC-EAD), gas chromatography coupled with mass spectrometry (GC-MS) and electroantennography (EAG). The results show that (Z)-9-tetradecenal acetate (Z9-14:Ac), (Z)-11-hexadecenyl acetate (Z11-16:Ac), (Z)-7-dodecenyl acetate (Z7-12:Ac) or (E)-7-dodecenyl acetate (E7-12:Ac) with a ratio of 100: 15.8: 3.9 induced EAD responses to varying degree: Z9-14:Ac elicited a strong EAD response, Z7-12:Ac or E7-12:Ac elicited a small but clear EAD response, while Z11-16:Ac elicited a weak EAD response. The further single sensillum recording (SSR) showed that Z9-14:Ac and Z7-12:Ac induced dose-dependent activities in two types (A and B) of sensilla in male antennae, respectively, while the sensilla in response to E7-12:Ac and Z11-16:Ac was not recorded. Finally, wind tunnel tests reveal that Z9-14:Ac and Z7-12:Ac are two principal sex pheromone components of the tested population. This article is protected by copyright. All rights reserved.

20.
Sheng Wu Gong Cheng Xue Bao ; 37(6): 1845-1857, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34227280

RESUMO

Non-ribosomal peptide synthetases catalyze the biosynthesis of structurally and functionally diverse non-ribosomal peptide natural products, which have broad applications in pharmaceutical, agricultural, and industrial sectors. Engineered non-ribosomal peptide synthetases can be used to produce novel non-ribosomal peptides through combinatorial biosynthesis. This conforms to the concept of green chemistry, thus attracts increasing attention across the world. Herein, three different engineering strategies were summarized, and recent advances in this field were reviewed.


Assuntos
Produtos Biológicos , Peptídeo Sintases , Engenharia de Proteínas , Peptídeo Sintases/genética , Peptídeos
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